1. Field of the Invention
The present invention relates to a method for producing (+)-estrone derivatives useful for oral contraceptives by using dicyclopentadiene derivatives as starting materials, and to intermediates which is used for the production of (+)-estrone derivatives.
2. Description of the Prior Art
(+)-Estrone is a compound useful for oral contraceptives, and it has been known from a long time to obtain the compound by methods in which natural materials are used (U.S. Pat. Nos. 1,967,350 (1934) and 135,992 (1962). However, the efficiency and yields of the methods are too inferior to those of synthetic methods to compare with.
Synthetic methods of (+)-estrone whose configuration is a natural type have been developed. Posner et al. (J. Am. Chem. Soc., 108,1239(1986) disclosed that a compound having an AB ring skeleton and a compound having a D ring skeleton which is asymmetrically derived are reacted by an asymmetric Michael addition reaction, and a C ring skeleton is formed by an intramolecular Diels-Alder reaction to construct an estron skeleton having a diastereo selectivity of 91-94%. However, the total yield is low, 6.3%, and the process has inefficiently nine steps.
Moreover, Taber et al. (J. Org. Chem.,52 28(1987)) constructed a .beta.-ketoester having a D ring skeleton by using a camphor derivative as a chiral source, combined the compound with a benzocyclobutene derivative, and constructed a BC ring skeleton by internal cyclization reaction in one step to synthesize (+)-estrone having an optical purity of 91% ee. However, the process has many reaction steps. To construct the .beta.-ketoester, it needs five steps. To synthesize the benzocyclobutene derivative, it needs three steps. To combine the both compounds and to obtain the objective skeleton, it needs three steps. The yield of the ring formation is low, 41%, and the total yield from the .beta.-ketoester precursor is 9.8%. The stereoselectivity of the (+)-estrone is comparatively good, but the efficciency of the process is no good.
Before the present invention, (+)-estrone was much in demand, but it was not provided well.